Orally administered drugs with relatively poor aqueous solubility can exhibit poor absorption in the gastrointestinal tract. The solubility of such drugs can often be improved by administering the drugs in the form of salts. On the other hand, some drug salts have relatively high solubility under certain pH conditions but convert to less soluble forms when the pH changes. Basic salts, for example, can be comparatively soluble in neutral or basic aqueous media, but can convert to a less soluble form under acidic conditions. When such drug salts are administered orally, their solubility can be lost or significantly reduced in the acidic conditions typically encountered in the stomach, leading again to poor absorption of the drug into the systemic circulation. On the other hand, acid salts can be comparatively soluble in strongly acidic media (e.g., pH<4), but convert to a less soluble form in less acidic conditions (e.g., pH of about 5 or higher). Oral administration of these drug salts can accordingly result in sufficient solubility in the stomach, but inadequate solubility in the less acidic environment of the intestinal tract, leading to poor overall absorption.
In some cases the problem can be overcome by administering a larger quantity of the drug salt (e.g., by increasing the size and/or frequency of the dose), so that an effective amount of the drug can enter circulation and reach the targeted site(s) in the body. A drawback to this approach is that it is wasteful of drug. Another drawback is that increasing the dose frequency can lead to inadvertent or intentional patient non-compliance with the drug regimen. In some cases, the insolubility problem is so severe that oral administration is not a practical option. Accordingly, there exists a need for new means that provide for the efficient and effective oral administration of such drugs and drug salts.